The Harvard/Boston City ACTU has four clinical centers for trials of promising drugs or drug combinations in the treatment of HIV-infection or its complications. The four centers are the Massachusetts General Hospital (MGH), Beth Israel Hospital (BIH), New England Deaconess Hospital (NEDH) and Boston City Hospital (BCH). This collaborative group draws from a wide patient catchment area in Massachusetts and throughout New England, including all socio-economic groups. Both sexes are represented and there is a wide diversity of racial and ethnic groups included in these studies. All adult risk groups participate, and the numbers of under-represented and minority population participants has risen steadily over recent years. Studies are conducted of anti-retrovirals, as well as of agents active against opportunistic pathogens, cancers, and metabolic or neurologic complications of HIV infection. Both Phase I and Phase II-III studies are performed. The current proposal is to expand these studies and to broaden the net of underrepresented populations included in clinical trials. Plans are described to continue expansion of studies into these groups. Harvard/Boston City is also applying to be a Center for Protocol Mandated Virology (Subproject 9002) and a Center for Developmental Research in Virology (Subproject #1). Our group has made major contributions to existing knowledge concerning HIV-1 and its role in AIDS, including the initial isolation of HIV-1 from genital secretions, monocyte-macrophages, and the central nervous system. Harvard has participated in the ACTG guality control program since its inception, and is conducting critical studies on viral resistance and quantitation. Plans are to expand our research programs on drug resistance of HIV-1, herpes simplex, and cytomegalovirus, as well as on PCR-based technology for HIV-1 quantitation.